Mesoscale organization of ventral and dorsal visual pathways in macaque monkey revealed by 7T fMRI.

In human and nonhuman primate brains, columnar (mesoscale) organization has been demonstrated to underlie both lower and higher order aspects of visual information processing. Previous studies have focused on identifying functional preferences of mesoscale domains in specific areas; but there has been little understanding of how mesoscale domains may cooperatively respond to single visual stimuli across dorsal and ventral pathways. Here, we have developed ultrahigh-field 7 T fMRI methods to enable simultaneous mapping, in individual macaque monkeys, of response in both dorsal and ventral pathways to single simple color and motion stimuli. We provide the first evidence that anatomical V2 cytochrome oxidase-stained stripes are well aligned with fMRI maps of V2 stripes, settling a long-standing controversy. In the ventral pathway, a systematic array of paired color and luminance processing domains across V4 was revealed, suggesting a novel organization for surface information processing. In the dorsal pathway, in addition to high quality motion direction maps of MT, MST and V3A, alternating color and motion direction domains in V3 are revealed. As well, submillimeter motion domains were observed in peripheral LIPd and LIPv. In sum, our study provides a novel global snapshot of how mesoscale networks in the ventral and dorsal visual pathways form the organizational basis of visual objection recognition and vision for action.

Visual experience-dependent development of ocular dominance columns in pigmented rats.

Despite previous agreement of the absence of cortical column structure in the rodent visual cortex, we have recently revealed a presence of ocular dominance columns (ODCs) in the primary visual cortex (V1) of adult Long-Evans rats. In this study, we deepened understanding of characteristics of rat ODCs. We found that this structure was conserved in Brown Norway rats, but not in albino rats; therefore, it could be a structure generally present in pigmented wild rats. Activity-dependent gene expression indicated that maturation of eye-dominant patches takes more than 2 weeks after eye-opening, and this process is visual experience dependent. Monocular deprivation during classical critical period strongly influenced size of ODCs, shifting ocular dominance from the deprived eye to the opened eye. On the other hand, transneuronal anterograde tracer showed a presence of eye-dominant patchy innervation from the ipsilateral V1 even before eye-opening, suggesting the presence of visual activity-independent genetic components of developing ODCs. Pigmented C57BL/6J mice also showed minor clusters of ocular dominance neurons. These results provide insights into how visual experience-dependent and experience-independent components both contribute to develop cortical columns during early postnatal stages, and indicate that rats and mice can be excellent models to study them.

Functional topography of pulvinar-visual cortex networks in macaques revealed by INS-fMRI.

The pulvinar in the macaque monkey contains three divisions: the medial pulvinar (PM), the lateral pulvinar (PL), and the inferior pulvinar (PI). Anatomical studies have shown that connections of PM are preferentially distributed to higher association areas, those of PL are biased toward the ventral visual pathway, and those of PI are biased with the dorsal visual pathway. To study functional connections of the pulvinar at mesoscale, we used a novel method called INS-fMRI (infrared neural stimulation and functional magnetic resonance imaging). This method permits studies and comparisons of multiple pulvinar networks within single animals. As previously revealed, stimulations of different sites in PL and PI produced topographically organized focal activations in visual areas V1, V2, and V3. In contrast, PM stimulation elicited little or diffuse response. The relative activations of areas V1, V2, V3A, V3d, V3v, V4, MT, and MST revealed that connections of PL are biased to ventral pathway areas, and those of PI are biased to dorsal areas. Different statistical values of activated blood-oxygen-level-dependent responses produced the same center of activation, indicating stability of connectivity; it also suggests possible dynamics of broad to focal responses from single stimulation sites. These results demonstrate that infrared neural stimulation-induced connectivity is largely consistent with previous anatomical connectivity studies, thereby demonstrating validity of our novel method. In addition, it suggests additional interpretations of functional connectivity to complement anatomical studies.

The Expression Patterns of Cytochrome Oxidase and Immediate-Early Genes Show Absence of Ocular Dominance Columns in the Striate Cortex of Squirrel Monkeys Following Monocular Inactivation.

Because at least some squirrel monkeys lack ocular dominance columns (ODCs) in the striate cortex (V1) that are detectable by cytochrome oxidase (CO) histochemistry, the functional importance of ODCs on stereoscopic 3-D vision has been questioned. However, conventional CO histochemistry or trans-synaptic tracer study has limited capacity to reveal cortical functional architecture, whereas the expression of immediate-early genes (IEGs), c-FOS and ZIF268, is more directly responsive to neuronal activity of cortical neurons to demonstrate ocular dominance (OD)-related domains in V1 following monocular inactivation. Thus, we wondered whether IEG expression would reveal ODCs in the squirrel monkey V1. In this study, we first examined CO histochemistry in V1 of five squirrel monkeys that were subjected to monocular enucleation or tetrodotoxin (TTX) treatment to address whether there is substantial cross-individual variation as reported previously. Then, we examined the IEG expression of the same V1 tissue to address whether OD-related domains are revealed. As a result, staining patterns of CO histochemistry were relatively homogeneous throughout layer 4 of V1. IEG expression was also moderate and homogeneous throughout layer 4 of V1 in all cases. On the other hand, the IEG expression was patchy in accordance with CO blobs outside layer 4, particularly in infragranular layers, although they may not directly represent OD clusters. Squirrel monkeys remain an exceptional species among anthropoid primates with regard to OD organization, and thus are potentially good subjects to study the development and function of ODCs.

Multiple Visuotopically Organized Subdivisions of the Lateral Pulvinar/Central Lateral Inferior Pulvinar Project into Thin and Thick Stripe Compartments of V2 in Macaques.

The lateral and central lateral inferior pulvinar (PL/PIcl) of primates has been implicated in playing an important role in visual processing, but its physiological and anatomical characteristics remain to be elucidated. It has been suggested that there are two complete visuotopic maps in the PL/PIcl, each of which sends afferents into V2 and V4 in primates. Given that functionally distinct thin and thick stripes of V2 both receive inputs from the PL/PIcl, this raises the possibility of a presence of parallel segregated pathways within the PL/PIcl. To address this question, we selectively injected three types of retrograde tracers (CTB-488, CTB-555, and BDA) into thin or thick stripes in V2 and examined labeling in the PL/PIcl in macaques. As a result, we found that every cluster of retrograde labeling in the PL/PIcl included all three types of signals next to each other, suggesting that thin stripe- and thick stripe-projecting compartments are not segregated into domains. Unexpectedly, we found at least five topographically organized retrograde labeling clusters in the PL/PIcl, indicating the presence of more than two V2-projecting maps. Our results suggest that the PL/PIcl exhibits greater compartmentalization than previously thought. They may be functionally similar but participate in multiple cortico-pulvinar-cortical loops.

Immunoreactivity of Vesicular Glutamate Transporter 2 Corresponds to Cytochrome Oxidase-Rich Subcompartments in the Visual Cortex of Squirrel Monkeys.

Cytochrome oxidase (CO) histochemistry has been used to reveal the cytoarchitecture of the primate brain, including blobs/puffs/patches in the striate cortex (V1), and thick, thin and pale stripes in the middle layer of the secondary visual cortex (V2). It has been suggested that CO activity is coupled with the spiking activity of neurons, implying that neurons in these CO-rich subcompartments are more active than surrounding regions. However, we have discussed possibility that CO histochemistry represents the distribution of thalamo-cortical afferent terminals that generally use vesicular glutamate transporter 2 (VGLUT2) as their main glutamate transporter, and not the activity of cortical neurons. In this study, we systematically compared the labeling patterns observed between CO histochemistry and immunohistochemistry (IHC) for VGLUT2 from the system to microarchitecture levels in the visual cortex of squirrel monkeys. The two staining patterns bore striking similarities at all levels of the visual cortex, including the honeycomb structure of V1 layer 3Bß (Brodmann's layer 4A), the patchy architecture in the deep layers of V1, the superficial blobs of V1, and the V2 stripes. The microarchitecture was more evident in VGLUT2 IHC, as expected. VGLUT2 protein expression that produced specific IHC labeling is thought to originate from the thalamus since the lateral geniculate nucleus (LGN) and the pulvinar complex both show high expression levels of VGLUT2 mRNA, but cortical neurons do not. These observations support our theory that the subcompartments revealed by CO histochemistry represent the distribution of thalamo-cortical afferent terminals in the primate visual cortex.